Breast Cancer Drug Shows Promise In Improving Leukemia Treatment

Researchers at Oregon Health and Science University (OHSU) have discovered a promising new drug combination that could significantly improve treatment for people with acute myeloid leukemia (AML), one of the most aggressive and deadly forms of blood cancer.

The study, published in the journal Cell Reports Medicine, shows that combining venetoclax — a commonly used leukemia drug — with palbociclib, a drug currently approved for breast cancer, produces much stronger and longer-lasting results than standard treatment alone. Importantly, the combination appears to overcome one of the biggest challenges in AML care i.e. drug resistance.

AML progresses rapidly and is often difficult to treat, especially in older patients. While new drugs have improved early treatment responses in recent years, long-term survival remains poor.

Venetoclax was approved by the U.S. Food and Drug Administration (FDA) in 2019 and quickly became a frontline treatment for AML when used with azacitidine, a chemotherapy drug. The combination has helped many patients achieve remission and improved quality of life. However, there is a major limitation.

“Unfortunately, almost all patients eventually develop resistance to treatment,” said Dr. Jeffrey Tyner, senior author of the study and a professor at OHSU’s School of Medicine. “Even with better initial responses, the five-year survival rate for AML is still only around 25 to 40 percent.”

Drug resistance means that cancer cells find ways to survive despite treatment, allowing the disease to return or progress. Overcoming this resistance is one of the most urgent needs in leukemia research.

To find better treatment options, the OHSU research team analyzed more than 300 AML patient samples and tested 25 different drug combinations. Among all the combinations studied, venetoclax paired with palbociclib stood out as the most effective.

Palbociclib is a drug that slows down cell division and is already widely used to treat certain types of breast cancer. While it had not been used in AML before, researchers suspected it might work because cancer cells often rely on similar survival mechanisms, even across different cancer types.

“Seeing how well this combination worked really motivated us to understand why,” said Dr. Melissa Stewart, lead author of the study. “It didn’t just work better — it appeared to stop the cancer cells from adapting and becoming resistant.”

The researchers discovered that when AML cells are treated with venetoclax alone, they try to survive by increasing protein production. This allows them to repair damage and continue growing despite the drug.

Palbociclib blocks this escape route. It interferes with the cell’s protein-making machinery, preventing leukemia cells from adapting to treatment.

“When we looked at patient samples that responded well to the combination, we saw a clear reduction in genes involved in protein production,” Stewart explained. “That was a major clue.”

Further analysis using a genome-wide CRISPR screen — a powerful genetic tool — confirmed that the two drugs work together to shut down multiple survival pathways at the same time. This makes it much harder for cancer cells to escape treatment.

The research team tested the drug combination not only in patient samples but also in mouse models implanted with human AML cells that carried genetic mutations known to cause resistance to venetoclax.

“In these models, venetoclax alone didn’t improve survival at all, which is exactly what we would expect,” Stewart said. “But when we added palbociclib, most of the mice lived for nearly a year. One mouse was still alive when the study ended.”

These findings suggest that the drug combination could be effective even in patients whose leukemia no longer responds to standard therapy.

For Stewart, the research is not only scientific but deeply personal. She is a breast cancer survivor who received treatment at OHSU.

“I know firsthand what it means to be a cancer patient,” she said. “The hope that comes from research and clinical trials is incredibly powerful. Working on this project gave me a way to give back.”

The researchers emphasized that this study highlights the importance of looking beyond traditional cancer categories.

“People may wonder why a breast cancer drug would work in leukemia,” Tyner said. “But many cancers share the same biological pathways. If we follow the data, it often leads us to unexpected but important discoveries.”

Encouraged by their findings, the team is now studying other drugs similar to palbociclib — many of which are already approved for breast cancer — to identify additional treatment options for AML. Because these drugs are already in use, moving them into clinical trials for leukemia could be faster than developing new medicines from scratch.

The combination of venetoclax and palbociclib has not yet been tested in people with AML. However, based on the strong laboratory and animal data, researchers are hopeful it could lead to more effective and durable treatments.

“Our prediction is that this approach could address many of the resistance mechanisms we currently see,” Tyner said. “Turning this into a treatment option for patients will take time and careful testing, but this is exactly why we do this work.”

If successful in clinical trials, the discovery could mark an important step forward in the fight against one of the toughest blood cancers — offering renewed hope to patients and families facing AML.